APC membrane recruitment protein 1; Amer1; protein FAM123B; Wilms tumor gene on the X chromosome protein (AMER1 FAM123B WTX)

Function

• regulator of the canonical Wnt signaling pathway
• specifically binds phosphatidylinositol 4,5-bisphosphate (Ptdins(4,5)P2), translocating to the cell membrane & interacting with key regulators of Wnt signaling, such as components of the beta-catenin destruction complex
• acts as a positive or negative regulator of Wnt signaling, depending on context:
  • a positive regulator by promoting LRP6 phosphorylation
  • a negative regulator by acting as a scaffold protein for the beta-catenin destruction complex & promoting stabilization of Axin at the cell membrane
• promotes CTNNB1 ubiquitination & degradation
• involved in kidney development
• interacts with CTNNB1, AXIN1, LRP6, KEAP1, APC & BTRC
• interacts with SCF E3 ligase complex containing BTRC &/or FBXW11
• identified in the beta-catenin destruction complex containing CTNNB1, APC, AXIN1 & AXIN2
• interacts with WT1

Structure

belongs to the Amer family

Compartment

• cytoplasm
• cell membrane, cytoplasmic side
• nucleus
• shuttles between nucleus & cytoplasm
• detected in nuclear paraspeckles that are found close to splicing speckles
• translocates to the cellmembrane following binding to Ptdins(4,5)P2

Alternative splicing

named isoforms=2

Expression

• detected in fetal & adult kidney, brain & spleen

Pathology

• defects in AMER1 are associated with osteopathia striata with cranial sclerosis
• inactivated in approximately 1/3 of Wilms tumors

More general terms

• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=139285
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:139285
• OMIM: https://mirror.omim.org/entry/300373
• OMIM: https://mirror.omim.org/entry/300647
• UniProt: http://www.uniprot.org/uniprot/Q5JTC6.html